AI Article Synopsis
- * A small-molecule inhibitor for SLC6A19 was discovered using two assays and a collection of 3440 compounds.
- * The compound cinromide was identified as a robust and selective inhibitor of SLC6A19, with additional analogs tested to support structure-activity relationship studies.
Article Abstract
SLC6A19 (BAT1) is a neutral amino acid transporter, the loss of function of which results in Hartnup disease. SLC6A19 is also believed to have an important role in amino acid homeostasis, diabetes, and weight control. A small-molecule inhibitor of human SLC6A19 (hSLC6A19) was identified using two functional cell-based assays: a fluorescence imaging plate reader (FLIPR) membrane potential (FMP) assay and a stable isotope-labeled neutral amino acid uptake assay. A diverse collection of 3440 pharmacologically active compounds from the Microsource Spectrum and Tocriscreen collections were tested at 10 µM in both assays using MDCK cells stably expressing hSLC6A19 and its obligatory subunit, TMEM27. Compounds that inhibited SLC6A19 activity in both assays were further confirmed for activity and selectivity and characterized for potency in functional assays against hSLC6A19 and related transporters. A single compound, cinromide, was found to robustly, selectively, and reproducibly inhibit SLC6A19 in all functional assays. Structurally related analogs of cinromide were tested to demonstrate structure-activity relationship (SAR). The assays described here are suitable for carrying out high-throughput screening campaigns to identify modulators of SLC6A19.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1177/2472555218794627 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Screening of high glucose tolerant Escherichia coli for L-valine fermentation by autonomous evolutionary mutation.
Appl Microbiol Biotechnol
January 2025
College of Marine and Bioengineering, Yancheng Institute of Technology, Yancheng, 224051, PR China.
L-valine holds wide-ranging applications in medicine, food, feed, and various industrial sectors. Escherichia coli, a pivotal strain in industrial L-valine production, features a concise fermentation period and a well-defined genetic background. This study focuses on mismatch repair genes (mutH, mutL, mutS, and recG) and genes associated with mutagenesis (dinB, rpoS, rpoD, and recA), employing a high-glucose adaptive culture in conjunction with metabolic modifications to systematically screen for superior phenotypes.
View Article and Find Full Text PDFComplementary Strategies to Identify Differentially Expressed Genes in the Choroid Plexus of Patients with Progressive Multiple Sclerosis.
Neuroinformatics
January 2025
Laboratory for Applied Genomics and Bioinnovations, Instituto Oswaldo Cruz - Fiocruz, Rio de Janeiro, RJ, Brazil.
Multiple sclerosis (MS) is a neurological disease causing myelin and axon damage through inflammatory and autoimmune processes. Despite affecting millions worldwide, understanding its genetic pathways remains limited. The choroid plexus (ChP) has been studied in neurodegenerative processes and diseases like MS due to its dysregulation, yet its role in MS pathophysiology remains unclear.
View Article and Find Full Text PDFComparison of the rhizospheric soil bacteriomes of Oryza sativa and Solanum melongena crop cultivars reveals key genes and pathways involved in biosynthesis of ectoine, lysine, and catechol meta-cleavage.
Funct Integr Genomics
January 2025
Department of Zoology, University of Gour Banga, Malda, 732103, India.
Rice (Oryza sativa L.), Poaceae family, forms staple diet of half of world's population, and brinjal (Solanum melongena L.), an important solanaceous crop, are consumed worldwide.
View Article and Find Full Text PDFCorrelation analysis of transcriptome and metabolomics and functional study of Galactinol synthase gene (VcGolS3) of blueberry under salt stress.
Plant Mol Biol
January 2025
College of Horticulture and Landscape, Tianjin Agricultural University, Tianjin, 300392, China.
Soil salinity poses a significant environmental challenge for the growth and development of blueberries. However, the specific mechanisms by which blueberries respond to salt stress are still not fully understood. Here, we employed a comprehensive approach integrating physiological, metabolomic, and transcriptomic analyses to identify key metabolic pathways in blueberries under salt stress.
View Article and Find Full Text PDFSelf-sufficient biocatalytic cascade for the continuous synthesis of danshensu in flow.
Appl Microbiol Biotechnol
January 2025
Department of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Freiestrasse 3, 3012, Bern, Switzerland.
A new strategy has been developed to successfully produce the active component danshensu ex vivo. For this purpose, phenylalanine dehydrogenase from Bacillus sphaericus was combined with the novel hydroxyphenylpyruvate reductase from Mentha x piperita, thereby providing an in situ cofactor regeneration throughout the conversion process. The purified enzymes were co-immobilized and subsequently employed in batch biotransformation, resulting in 60% conversion of 10 mM L-dopa within 24 h, with a catalytic amount of NAD as cofactor.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!